The adipokine zinc-α2-glycoprotein activates AMP kinase in human primary skeletal muscle cells

Abstract

Context: Zinc-α2-glycoprotein (ZAG) induces lipid mobilization in adipose tissue (AT) and stimulates energy utilization in AT and skeletal muscle by up-regulation of UCP isoforms and GLUT4.

Objective: Our study aimed to investigate whether ZAG activates AMPKα, an important regulator of energy metabolism, in human skeletal muscle cells (SkMc).

Materials and Methods: SkMc were treated with recombinant ZAG, and activation of AMPKα and ACC, protein abundance of GLUT4, and UCP2 and UCP3 gene expression were analysed.

Results: Treatment of SkMc with ZAG induced short-time phosphorylation of AMPKα and ACC. Furthermore, AMPKα phosphorylation was elevated after 24 h, while for ACC no activation was observed. GLUT4 level was increased by 1.3-fold. However, UCP2 and UCP3 expression remained unaltered.

Discussion and Conclusion: These results show that ZAG leads to phosphorylation of AMPKα and ACC, thereby activating a pathway central to the regulation of energy metabolism. This mechanism may be involved in mediating the effects of ZAG in relation to increased energy utilization.

Acknowledgements

This work was supported by the Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen (Ministry of Science and Research of the State of North Rhine-Westphalia), the Bundesministerium für Gesundheit (Federal Ministry of Health), the UK Biotechnology and Biological Sciences Research Council (BBE015379), and European Union COST Action BM0602. The secretarial assistance of B. Hurow is gratefully acknowledged.

Declaration of interest

The authors report no declarations of interest.